Advances in the last decade have transformed HIV-1 infection into a chronic disease through the use of highly active antiretroviral (ARV) therapy. Recent studies suggest the ARVs used as pre-exposure prophylaxis (PrEP) to prevent HIV infection have the potential to transform the HIV pandemic. However, the success of ARVs in both the treatment and prevention of HIV is critically dependent on taking medications exactly as prescribed (adherence). To date, no reliable, accurate measurement for ARV adherence exists. This proposal will evaluate the use of a novel sensor platform termed the Digital Health Feedback System (DHFS) for real- time adherence monitoring in HIV-infected persons starting ARVs and in persons at high risk for HIV infection starting PrEP. Aim 1: Develop selected digitized ARVs for use within the DHFS. We will combine an edible sensor with commonly used ARVs within a gelcap to allow the DHFS to detect when a person takes their medication. Outcomes will include successful development of a `digitized' panel of ARVs to use with the DHFS, which are tested against USP guidelines and safe for use in clinical settings. Aim 2: Evaluate the use, acceptability, validity, and utility of the DHFS for longitudinal monitoring of adherence during initial ARV therapy. We will assess if the DHFS is acceptable to persons living with HIV that are initiating ARV treatment for the first time. Outcomes include acceptabilit as measured through validated questionnaires and persistence of use by participants, positive detection accuracy of the DHFS as measured by directly observed ingestions at study visits, and medication adherence as measured by DHFS. Aim 3: Evaluate the acceptability, validity, and utility of the DHFS for longitudinal monitoring of ARVs used in HIV pre-exposure prophylaxis (PrEP). We will assess if the DHFS is acceptable to persons at high risk for HIV infection that are initiating PrEP. Outcomes include acceptability as measured through validated questionnaires and persistence of use by participants, positive detection accuracy of the DHFS as measured by directly observed ingestions at study visits, and medication adherence as measured by DHFS.